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Hematopoietic Stem Cell Transplantation. Lynn Savoie September 30, 2006. Hematopoietic stem cell transplantation is potentially life-saving therapy in patients with SAA or MDS Generally done when benefits thought to outweigh risks

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hematopoietic stem cell transplantation

Hematopoietic Stem Cell Transplantation

Lynn Savoie

September 30, 2006

slide2
Hematopoietic stem cell transplantation is potentially life-saving therapy in patients with SAA or MDS
  • Generally done when benefits thought to outweigh risks
  • Only allogeneic stem cell transplantation considered for these diseases therefore need a donor
  • Recipient and donor factors considered when assessing risk
general concept
General Concept
  • Blood cell production and immune system very closely linked and ultimately derived from bone marrow
  • Goal of high dose chemotherapy is to kill “defective” marrow – MDS or malfunctioning immune system – SAA
  • Replace with healthy marrow/immune system
    • Unfortunately not straightforward – mostly due to the new immune system
risks
Risks
  • Infections
    • Potentially life or organ threatening
      • Due to neutropenia then immunosupression
  • Graft versus host disease
    • New immune system attacking recipient organs
    • Acute and chronic
      • Can affect many different organs
    • Potentially life or organ threatening
    • Potentially life altering
  • Graft failure
    • Rare but potentially fatal
      • Increased risk in aplastic anemia
types of transplants

Types of transplants

3 main factors

slide6
Type of donor
    • Related
    • Unrelated
  • Source of stem cell
    • Bone marrow
    • Peripheral blood
    • Cord blood
  • Conditioning Regimens
    • Myeloablative
    • Non-myeloablative
    • TBI containing
type of donor

Type of donor

Related vs. Unrelated

slide9
HLA antigens
    • Proteins that help the immune system identify self vs. non-self
    • Genetically inherited together on chromosome 6
    • Most important determinant of compatibility between donor and recipient
    • Each sibling pair has a 25% chance of inheriting the same HLA antigens
    • Approximately 30% of patients will have an HLA matched sibling
slide11
Statistically unlikely for an extended family member to have 2 similar HLA groupings to patient just by chance
  • Able to find a unrelated donor in 70% of cases that is fully matched but not likely “identical”
  • Search can take time
  • More difficult in some ethnic groups due to genetic diversity
  • Generally increased and more severe graft versus host disease than with related donor
other important factors in donor selection
Other important factors in donor selection
  • Age
    • Younger generally better
  • Sex
    • Males generally better
  • Number of pregnancies
    • Few the better
  • Blood group
    • Same is better
  • CMV status
    • Negative donor is best if patient is negative
  • Health
    • Some health conditions preclude donation from a recipient perspective and some from a donor perspective
source of stem cell

Source of Stem Cell

Bone marrow vs. peripheral blood vs. cord blood

slide14
Still unclear whether bone marrow or peripheral blood stem cells better for recipients – studies ongoing
    • Currently using bone marrow in SAA and peripheral blood in MDS
  • Faster count recovery with peripheral blood stem cells but increase chronic graft versus host disease that may or may not translate into decreased relapse
  • Peripheral blood collection generally felt to be easier for donor but long term effects of G-CSF not known
cord blood stem cells
Cord Blood Stem Cells
  • Rapidly available
  • Can accept a lesser match
  • Less graft versus host disease
    • Immune cells naive
  • Cell doses often a concern in adults
    • Because based on weight
  • Longer time to count recovery
    • can increase risk of infection due to prolonged neutropenia
  • Combinations or expansion being investigated
conditioning regimens

Conditioning Regimens

Myeloablative vs. Non-myeloablative vs. TBI containing

slide17
Myeloablative
    • Generally used for SAA or MDS
    • Calgary regimens somewhat less myeloablative than other regimens…..but not technically non-myeloablative
  • Non-myeloablative
    • Unclear if really safer – generally more graft vs. host disease, particularly chronic due to mixture of cells present
    • Unclear if really a role in these disorders since don’t need much graft vs. leukemia effect-under investigation
  • TBI containing
    • Used in acute leukemia and at times in MDS if transforming – felt to decrease relapse
calgary flubup tbi
Calgary – FLUBUP +/- TBI
  • From 05/99 to 05/05
  • Matched related donor (MRD)
    • 201 pts, survival 60%
  • Mismatched related donor (MMRD)
    • 22 pts, survival 58%
  • Matched unrelated donor (MUD)
    • 81 pts, survival 57%
  • Mismatched unrelated donor (MMUD)
    • 40 pts, survival 38%
calgary
Calgary
  • MDS
    • MRD – 15 pts
      • Survival 79%
    • Alt – 10 pts
      • Survival 38%
  • SAA
    • MRD -20 pts
      • survival 90%, 100% in last 13 yrs
    • Alt – 10 pts
      • survival 38%
slide25
Myelodysplasia
    • Patients < 65 yrs of age
    • Before transfusion dependence and/or clinically significant neutropenia
    • Before transformation to acute leukemia
  • Severe aplastic anemia
    • If pt < 40 y.o. with sib match
    • If >60 y.o. pt > 40 y.o. with sib match trial after failure of immunosupression
    • No sib match – Failure of immunosupression X 2, consider after 1 if pt is young
donor search
Donor Search
  • Type sibling at presentation if HSCT at all a consideration now or later
  • Can identify an unrelated donor when HSCT strongly under consideration
    • Costs
    • Can only “hold” a donor for 3 months
ubmdr
UBMDR
  • Established in 1989
  • Administered by Canadian Blood Services
  • 215 000 potential volunteer donors
  • If no Canadian donor can search the world
slide28
NMDP
  • United States
  • 6 million donors
  • 50 000 cord blood units
bone marrow donors worldwide
Bone Marrow Donors Worldwide
  • As of August 22, 2006 – 10 733 542 donors and cord blood units
  • 58 stem cell donor registries from 43 countries
  • 38 cord blood banks from 21 countries
  • 571 users from 420 organizations